After total knee arthroplasty, changes in articular surface geometry, soft tissue treatment, and component alignment can alter normal lower limb function. The guided motion bi‐cruciate substituting prosthesis was designed specifically to restore physiological knee joint motion. We determined whether this design could in vivo normal kinematics and kinetics, not only at the replaced knee, but also throughout both lower limbs. Sixteen patients (4 male, 12 female, mean age of 68.2 years with a range from 58 to 79 years) with primary knee osteoarthritis were implanted with the bi‐cruciate substituting prosthesis. At 6‐month follow‐up, knee joint kinematics was assessed by video‐fluoroscopy during stair‐climbing, chair‐rising/sitting, and step‐up/down. Lower limb overall function was also assessed on the same day by standard gait analysis with simultaneous electromyography during level walking. By video‐fluoroscopy, mean anteroposterior translations between femoral and tibial components during the three motor tasks were 9.7 ± 3.0, 10 ± 2.6, and 6.9 ± 3.5 mm on the medial compartment, and 14.3 ± 3.5, 18.5 ± 3.0, and 13.9 ± 3.8 mm on the lateral compartment, respectively. Axial rotation ranged from 5.6° to 26.2°. Gait analysis revealed restoration of nearly normal walking patterns in most patients. This rare combination of measurements, i.e., accurate rotation‐translation at the replaced knee and complete locomotion patterns at both lower limb joints, suggested that bi‐cruciate substituting arthroplasty can restore physiological knee motion and normal overall function. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1569–1575, 2009